基于网络药理学和分子对接法探索藿香正气口服液预防新型冠状病毒肺炎(COVID-19)活性化合物研究

Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019(COVID-19) based on network pharmacology and molecular docking

目的采用网络药理学与分子对接法探索藿香正气口服液预防新型冠状病毒肺炎(COVID-19)的活性化合物。方法借助中药系统药理学分析平台(TCMSP)检索藿香正气口服液组方中苍术、陈皮、厚朴、白芷、茯苓、大腹皮、半夏、甘草、广藿香、紫苏的化学成分和作用靶点。通过Uniprot数据库查询靶点对应的基因,进而运用Cyoscape3.7.2软件构建药材-化合物-靶点(基因)网络进行可视化,通过DAVID进行GO功能富集分析和KEGG通路富集分析,预测其作用机制,并通过Prism软件及Omicshare数据库绘制柱状图及气泡图进行可视化。结果药材-化合物-靶点网络包含了10种药材,123个化合物和相应靶点基因257个,关键靶点基因涉及PTGS2、HSP90AB1、AR、CAMSAP2、PPARG、NOS2等。GO功能富集分析得到GO条目278个(P<0.05),其中生物过程(BP)条目178个,细胞组成(CC)条目36个,分子功能(MF)条目64个。KEGG通路富集分析筛选得到119条信号通路(P<0.05),涉及乙型肝炎、小细胞肺癌、非小细胞肺癌、膀胱癌、前列腺癌及T细胞受体通路等。分子对接结果显示槲皮素、异鼠李素、葛花苷元、山柰酚、汉黄芩素、黄芩素等核心化合物与COVID-19推荐药的亲和力相似。其中以槲皮素、异鼠李素、葛花苷元3者亲和力最强。结论藿香正气口服液中的化合物能通过与血管紧张素转化酶II(ACE2)结合作用于PTGS2、HSP90AB1、AR、CAMSAP2等靶点调节多条信号通路,从而发挥对COVID-19的防治作用。

Objective To explore the active compounds of Huoxiang Zhengqi Oral Liquid for the treatment of coronavirus desease 2019(COVID-19)by network pharmacology and molecular docking.Methods The chemical constituents and action targets of Atractylodes chinensis,Citrus reticulata,Magnolia officinalis,Angelica dahurica,Poria cocos,Areca catechu,Pinellia ternata,Glycyrrhiza uralensis,Pogostemon cablin and Perilla frutescens were retrieved from TCMSP.Uniprot database was used to search the corresponding genes of targets,then Cyoscape 3.7.2 software was used to construct the network of medicinal materials-compound-target(gene)for visualization;GO function enrichment analysis and KEGG pathway enrichment analysis were performed through DAVID to predict its mechanism of action,and histograms and bubble maps were plotted by Prism software and Omicshare database for visualization.Results The network of medicinal materials-compound-target contained 10 medicinal materials,123 compounds and 257 corresponding target genes,and the key target genes involved PTGS2,HSP90 AB1,AR,CAMSAP2,PPARG,NOS2,etc.GO functional enrichment analysis resulted in 278 GO entries(P<0.05),including 178 biological processes(BP)entries and 36 cellular component(CC)entries,and 64 molecular function(MF)entries.KEGG pathway enrichment analysis revealed that there were 119(P<0.05)signaling pathways involving Hepatitis B,small cell lung cancer,non-small cell lung cancer,bladder cancer,prostate cancer and T cell receptor pathways.The results of molecular docking showed that the core compounds such as quercetin,isorhamnetin,irisolidone,kaempferol,wogonin,and baicalein were similar in affinity with the COVID-19 recommended medicine.Among them,quercetin,isorhamnetin and irisolidone had the strongest affinity.Conclusion The compounds in Huoxiang Zhengqi Oral Liquid can combine with angiotensin converting enzyme II(ACE2)binding to PTGS2,HSP90 AB1,AR,CAMSAP2 and other targets to regulate multiple signaling pathways,thus exerting a preventive or therapeutic effect on COVID-19.